Denaturing high-performance liquid chromatography screening of the long QT syndrome-related cardiac sodium and potassium channel genes and identification of novel mutations and single nucleotide polymorphisms
Journal
Journal of Human Genetics
Journal Volume
50
Journal Issue
9
Pages
490-496
Date Issued
2005
Author(s)
Su Y.-N.
Yeh S.-J.
Wang C.-C.
Ko Y.-L.
Wu T.-J.
Ueng K.-C.
Lei M.-H.
Tsao H.-M.
Chen S.-A.
Lin T.-K.
Lo H.-M.
Huang S.K.S.
Abstract
Mutations in cardiac potassium and sodium channel genes are responsible for several hereditary cardiac arrhythmia syndromes. We established a denaturing high-performance liquid chromatography (DHPLC) protocol for rapid mutation screening of these genes, and reported mutations and variations identified by this method. We included 28 patients with Brugada syndrome, 4 with congenital long QT syndrome (LQTS), 11 with drug-induced LQTS, 4 with idiopathic ventricular fibrillation, and 50 normal volunteers. Polymerase chain reactions were performed to amplify the entire coding region of these genes. DHPLC was used to screen for heteroduplexes then DNA sequencing was performed. With this method, we identified the mutation(s) in all four patients with congenital LQTS (KCNQ1 A341V, KCNH2 N633D, KCNH2 2768Cdel and KCNE1 K70 N Y81C double mutations). We also identified the SCN5A A551T mutation in 1 of the 28 patients with Brugada syndrome. All the above-mentioned mutations were novel except KCNQ1 A341V. No mutations were identified in patients with drug-induced LQTS or idiopathic ventricular fibrillation. In total, 25 single nucleotide polymorphisms were identified, 10 of which were novel. In conclusion, DHPLC is a sensitive and rapid method for detection of cardiac sodium and potassium channel gene mutations. ? The Japan Society of Human Genetics and Springer-Verlag 2005.
SDGs
Other Subjects
potassium channel; sodium channel; article; Brugada syndrome; clinical article; clinical protocol; congenital disorder; controlled study; denaturing high performance liquid chromatography; diagnostic accuracy; diagnostic value; DNA sequence; drug induced disease; female; gene amplification; gene identification; gene mutation; genetic screening; genetic variability; heart ventricle fibrillation; heteroduplex analysis; human; idiopathic disease; long QT syndrome; male; nucleotide sequence; polymerase chain reaction; single nucleotide polymorphism; volunteer
Type
journal article